Anti-inflammatory drugs, such as aspirin, indomethacin, ibuprofen, meclofenamate, naproxen, phenylbutazone, piroxicam and various corticosteroids are effective in treating or controlling pain, including headache, and in decreasing joint swelling, tenderness, pain and stiffness in conditions such as rheumatoid arthritis. Unfortunately, although such anti-inflammatory drugs are effective in treating pain and inflammatory conditions, they cause development of gastrointestinal ulcers thereby seriously limiting chronic use of these drugs.
It has now been found that when an anti-inflammatory drug is used in combination with a thromboxane A.sub.2 receptor antagonist, the anti-inflammatory drug is still effective in treating inflammation, while the thromboxane A.sub.2 receptor antagonist is effective in inhibiting and/or treating gastric erosion and/or gastrointestinal ulcers which may result from treatment with the anti-inflammatory drug. Thus, in effect, thromboxane A.sub.2 receptor antagonists are useful for the prevention and treatment of gastric and intestinal lesions in response to anti-inflammatory drugs.
U.S. Pat. No. 4,582,854 to Hall et al, discloses 7-oxabicycloheptane substituted oxa prostaglandin analogs having the structure ##STR1## wherein R is hydrogen, lower alkyl, alkali metal or trihydroxymethylaminomethane, R.sup.1 is lower alkyl, aryl, aralkyl, cycloalkyl or cycloalkylalkyl, R.sup.2 is hydrogen or lower alkyl, A is --CH.dbd.CH-- or --(CH.sub.2).sub.2 --, n is 1 to 4, and m is 1 to 8.
The Hall et al compounds are disclosed as being selective thromboxane A.sub.2 receptor antagonists and certain of these compounds are also thromboxane synthetase inhibitors or cyclooxygenase inhibitors, or anti-inflammatory agents in the manner of aspirin and indomethacin.
Mochizuki et al, "Thromboxane A.sub.2 Antagonistic Action of a New Anti-Ulcer Agent, Azuletil Sodium (KT1-32)," Scand. J. Gastroenterol 1989, 24 (suppl 162), 194-197 disclose that KT1-32 (sodium 3-ethyl-7-(1-methylethyl)-1-azulenesulfonate), a competitive TXA.sub.2 /PGH.sub.2 receptor antagonist "may be a promising drug for the treatment of peptic ulcers accompanied by hemorrhage (page 197)."